Gabriel, Elke, Ramani, Anand, Karow, Ulrike, Gottardo, Marco ORCID: 0000-0001-8649-7799, Natarajan, Karthick, Gooi, Li Ming, Goranci-Buzhala, Gladiola, Krut, Oleg, Peters, Franziska, Nikolic, Milos ORCID: 0000-0003-0029-7601, Kuivanen, Suvi, Korhonen, Essi ORCID: 0000-0003-4730-7715, Smura, Teemu ORCID: 0000-0002-9187-3151, Vapalahti, Olli ORCID: 0000-0003-2270-6824, Papantonis, Argyris ORCID: 0000-0001-7551-1073, Schmidt-Chanasit, Jonas, Riparbelli, Maria, Callaini, Giuliano ORCID: 0000-0003-2252-0309, Kroenke, Martin, Utermoehlen, Olaf and Gopalakrishnan, Jay (2017). Recent Zika Virus Isolates Induce Premature Differentiation of Neural Progenitors in Human Brain Organoids. Cell Stem Cell, 20 (3). S. 397 - 412. CAMBRIDGE: CELL PRESS. ISSN 1875-9777

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Abstract

The recent Zika virus (ZIKV) epidemic is associated with microcephaly in newborns. Although the connection between ZIKV and neurodevelopmental defects is widely recognized, the underlying mechanisms are poorly understood. Here we show that two recently isolated strains of ZIKV, an American strain from an infected fetal brain (FB-GWUH-2016) and a closely-related Asian strain (H/PF/2013), productively infect human iPSC-derived brain organoids. Both of these strains readily target to and replicate in proliferating ventricular zone (VZ) apical progenitors. The main phenotypic effect was premature differentiation of neural progenitors associated with centrosome perturbation, even during early stages of infection, leading to progenitor depletion, disruption of the VZ, impaired neurogenesis, and cortical thinning. The infection pattern and cellular outcome differ from those seen with the extensively passaged ZIKV strain MR766. The structural changes we see after infection with these more recently isolated viral strains closely resemble those seen in ZIKV-associated microcephaly.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Gabriel, ElkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramani, AnandUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karow, UlrikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gottardo, MarcoUNSPECIFIEDorcid.org/0000-0001-8649-7799UNSPECIFIED
Natarajan, KarthickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gooi, Li MingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goranci-Buzhala, GladiolaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krut, OlegUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peters, FranziskaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nikolic, MilosUNSPECIFIEDorcid.org/0000-0003-0029-7601UNSPECIFIED
Kuivanen, SuviUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Korhonen, EssiUNSPECIFIEDorcid.org/0000-0003-4730-7715UNSPECIFIED
Smura, TeemuUNSPECIFIEDorcid.org/0000-0002-9187-3151UNSPECIFIED
Vapalahti, OlliUNSPECIFIEDorcid.org/0000-0003-2270-6824UNSPECIFIED
Papantonis, ArgyrisUNSPECIFIEDorcid.org/0000-0001-7551-1073UNSPECIFIED
Schmidt-Chanasit, JonasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riparbelli, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Callaini, GiulianoUNSPECIFIEDorcid.org/0000-0003-2252-0309UNSPECIFIED
Kroenke, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Utermoehlen, OlafUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gopalakrishnan, JayUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-236852
DOI: 10.1016/j.stem.2016.12.005
Journal or Publication Title: Cell Stem Cell
Volume: 20
Number: 3
Page Range: S. 397 - 412
Date: 2017
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1875-9777
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CELL-CYCLE; CEREBRAL ORGANOIDS; MOUSE-BRAIN; STEM-CELLS; CEP152; MUTATIONS; INFECTION; NEURONS; BIOLOGY; MITOSISMultiple languages
Cell & Tissue Engineering; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/23685

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